The aim of this program is to demonstrate the applicability and development of new synthetic principles and reactions to problems in organic chemistry related to chemotherapeutically important compounds. The new routes developed will lead to practical approaches to macrolides, steroids, prostanoids, and various other natural products of biological significance. The use of transition metal templates to exercise chemoselectivity, regioselectivity, and stereocontrol in an absolute and relative sense constitutes a major aspect of this proposal. Macrocyclic compounds including macrolide antibiotics (e.g. erythromycin, zearalenone, etc.) and anti-tumor agents (e.g. jatrophone) will be explored. The metabolites of Vitamin D, the active forms of the vitamin, will involve new methods of cyclization, control of acyclic geometry, and control of stereochemistry. A chiral synthesis of steroids (e.g. estrone, testosterone, etc.) uses these templates. An enantioconvergent synthesis of prostanoids will allow access to this important class of compounds in optically pure form. Small ring chemistry and sulfur chemistry will contribute to these efforts. Completion of the total synthesis of the antibiotics pentalenolactone and hirsutic acid will be attempted. Application of these new principles to other classes of biologically important compounds will be considered.